PT  - JOURNAL ARTICLE
AU  - Yang, Hyunwon
AU  - Youm, Yun-Hee
AU  - Vandanmagsar, Bolormaa
AU  - Ravussin, Anthony
AU  - Gimble, Jeffrey M.
AU  - Greenway, Frank
AU  - Stephens, Jacqueline M.
AU  - Mynatt, Randall L.
AU  - Dixit, Vishwa Deep
TI  - Obesity Increases the Production of Proinflammatory Mediators from Adipose Tissue T Cells and Compromises TCR Repertoire Diversity: Implications for Systemic Inflammation and Insulin Resistance
AID  - 10.4049/jimmunol.1000021
DP  - 2010 Aug 01
TA  - The Journal of Immunology
PG  - 1836--1845
VI  - 185
IP  - 3
4099  - http://www.jimmunol.org/content/185/3/1836.short
4100  - http://www.jimmunol.org/content/185/3/1836.full
SO  - J. Immunol.2010 Aug 01; 185
AB  - Emerging evidence suggests that increases in activated T cell populations in adipose tissue may contribute toward obesity-associated metabolic syndrome. The present study investigates three unanswered questions: 1) Do adipose-resident T cells (ARTs) from lean and obese mice have altered cytokine production in response to TCR ligation?; 2) Do the extralymphoid ARTs possess a unique TCR repertoire compared with lymphoid-resident T cells and whether obesity alters the TCR diversity in specific adipose depots?; and 3) Does short-term elimination of T cells in epididymal fat pad without disturbing the systemic T cell homeostasis regulate inflammation and insulin-action during obesity? We found that obesity reduced the frequency of naive ART cells in s.c. fat and increased the effector-memory populations in visceral fat. The ARTs from diet-induced obese (DIO) mice had a higher frequency of IFN-γ+, granzyme B+ cells, and upon TCR ligation, the ARTs from DIO mice produced increased levels of proinflammatory mediators. Importantly, compared with splenic T cells, ARTs exhibited markedly restricted TCR diversity, which was further compromised by obesity. Acute depletion of T cells from epididymal fat pads improved insulin action in young DIO mice but did not reverse obesity-associated feed forward cascade of chronic systemic inflammation and insulin resistance in middle-aged DIO mice. Collectively, these data establish that ARTs have a restricted TCR-Vβ repertoire, and T cells contribute toward the complex proinflammatory microenvironment of adipose tissue in obesity. Development of future long-term T cell depletion protocols specific to visceral fat may represent an additional strategy to manage obesity-associated comorbidities.